Dendritic cells (DC) are professional antigen presenting cells that regulate innate and adaptive immunity. The role of fatty-acid synthesis in DC development and function is uncertain. We found that blockade of fatty-acid synthesis markedly decreases dendropoiesis in the liver and in primary and secondary lymphoid organs in mice. Human DC development from PBMC precursors was also diminished by blockade of fatty-acid synthesis. This was associated with higher rates of apoptosis in precursor cells and increased expression of Cleaved Caspase 3 and BCL-xL, and down-regulation of Cyclin B1. Further, blockade of fatty-acid synthesis decreased DC expression of MHCII, ICAM-1, B7-1, B7-2 but increased their production of selected pro-inflammatory cytokines including IL-12 and MCP-1. Accordingly, inhibition of fatty-acid synthesis enhanced DC capacityto activate allogeneic as well as antigen-restricted CD4+ and CD8+ T cells and induce CTL responses. Further, blockade of fatty-acid synthesis increased DC expression of Notch ligands and enhanced their ability to activate NK cell immune-phenotype and IFN-γ production. Since endoplasmic reticular (ER)-stress can augment the immunogenic function of APC, we postulated that this may account for the higher DC immunogenicity. We found that inhibition of fatty-acid synthesis resulted in elevated expression of numerous markers of ER stress in humans and mice and was associated with increased MAP kinase and Akt signaling. Further, lowering ER-stress by 4-phenylbutyrate mitigated the enhanced immune-stimulation associated with fatty-acid synthesis blockade. Our findings elucidate the role of fatty-acid synthesis in DC development and function and have implications to the design of DC vaccines for immunotherapy.

Objectives Opioid pain reliever (OPR) prescribing at Emergency Department (ED) discharge has increased in the past decade but specific prescription details are lacking. Prior ED OPR prescribing estimates relied on national survey extrapolation or prescription databases. The main goal of this study was to utilize a research consortium to analyze the characteristics of patients and opioid prescriptions using a national sample of ED patients. We also aimed to examine the indications for OPR prescribing, characteristics of opioids prescribed both in the ED and at the time of discharge, and characteristics of patients who received OPRs compared with those who did not. Methods This observational, multi-centered, retrospective cohort study assessed OPR prescribing to consecutive patients presenting to the consortium EDs during 1 week in October 2012. The consortium study sites consisted of 19 EDs representing 1.4 million annual visits, varied geographically, and were predominantly academic centers. Medical records of all patients aged 18-90 years discharged with an OPR (excluding tramadol) were individually abstracted via standardized chart review by investigators for detailed analysis. Descriptive statistics were generated. Results During the study week, 27,516 patient visits were evaluated in the consortium EDs. 19,321 (70.2%) were discharged and 3,284 patients (11.9% of all patients and 17.0% of discharged patients) received an OPR prescription. For those prescribed an OPR, mean age was 41.1 (SD 14.7) years and 1,694 (51.6%) were female. Mean initial pain score was 7.7 (SD 2.4). The most common diagnoses associated with OPR prescribing were back pain (10.2%), abdominal pain (10.1%), and extremity fracture (7.1%) or sprain (6.5%). The most common OPRs prescribed were oxycodone (52.3%), hydrocodone (40.9%) and codeine (4.8%). >99% were immediate release, 90.0% were combination preparations, and the mean and median number of pills was 16.6 (SD 7.6) and 15 (IQR=12-20) respectively. Conclusion In a study of ED patients treated over a single week across the country, 17% of discharged patients were prescribed OPRs. The majority of the prescriptions had small pill counts and almost exclusively immediate release formulations.

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Background Widespread vaccination is an essential component of the public health response to the COVID‐19 pandemic, yet vaccine hesitancy remains pervasive. This prospective survey investigation aimed to measure the prevalence of vaccine hesitancy in a patient cohort at two urban Emergency Departments (EDs) and characterize underlying factors contributing to hesitancy. Methods Adult ED patients with stable clinical status (Emergency Severity Index 3‐5) and without active COVID‐19 disease or altered mental status were considered for participation. Demographic elements were collected, as well as reported barriers/concerns related to vaccination and trusted sources of health information. Data were collected in‐person via a survey instrument proctored by trained research assistants. Results 1,555 patients were approached, and 1,068 patients completed surveys (completion rate 68.7%). Mean age was 44.1 y (SD 15.5, range 18‐93), 61% were female, and 70% were Black. 31.6% of ED patients reported vaccine hesitancy. Of note, 19.7% of the hesitant cohort were healthcare workers. In multivariable regression analysis, Black race (OR 4.24, 95%CI 2.62‐6.85) and younger age (age 18‐24 y, OR 4.57, 95%CI 2.66‐7.86; age 25‐35 y, OR 5.71, 95% CI 3.71‐8.81) were independently associated with hesitancy, to a greater degree than level of education (high school education or less, OR 2.27, 95%CI 1.23‐4.19). Hesitant patients were significantly less likely to trust governmental sources of vaccine information than non‐hesitant patients (39.6% vs 78.9%, p<0.001); less difference was noted in the domain of trust towards friends/family (51.1% vs. 61.0%, p=0.004). Hesitant patients also reported perceived vaccine safety concerns and perceived insufficient research. Conclusions Vaccine hesitancy is common among ED patients, and more common among Black and younger patients, independent of education level. Hesitant patients report perceived safety concerns and low trust in government information sources, but less so friends or family. This suggests strategies to combat hesitancy may need tailoring to specific populations.

Fall height and work-related falls were significantly associated with death on impact. This is a public health issue, as 13% of falls were work related and 4% of falls were due to improper use of safety equipment. Some work-related falls are potentially preventable with proper safety equipment use. Understanding patterns of injury may play a role in prevention and management of survivors in the acute period.